Increased extracellular volume, reduced stress perfusion, and worse systolic function in Wilson's disease

Wilson's disease (WD) causes intracellular copper accumulation due to a genetic defect in the copper-transporting protein ATP7B. Cardiac involvement has been reported even in young WD patients; however, pathophysiological mechanisms remain unclear. This study aimed to comprehensively assess the myocardium in WD patients without cardiac symptoms using multiparametric cardiovascular magnetic resonance imaging (CMR), including quantitative stress perfusion mapping and strain analysis.

WD patients and healthy volunteers underwent multiparametric 1.5T CMR, including cine, native T1, native T2, extracellular volume (ECV), adenosine stress perfusion mapping, and late gadolinium enhancement (LGE) imaging. Left and right ventricle (LV, RV) mass and volumes, global native T1, native T2, ECV, rest and stress perfusion, myocardial perfusion reserve (MPR), strain measures and liver native T1 were compared. LGE images were assessed visually. Disease type and duration, medications, and cardiovascular risk factors were recorded. Symptoms of myocardial ischemia were quantified with Seattle Angina Questionnaire-7.

WD patients (n = 17, 34 [29-55] years, 8/17 (47%) female) and healthy volunteers (n = 17, 33 [29-52] years, 8/17 (47%) female, p = ns for both) were included. There were no differences in cardiovascular risk factors or medications. LV ejection fraction was lower in WD patients (57 [55-61] vs 62 [57-67] %, p = 0.02), and LV global circumferential strain was mildly worse (-18 [-19 to (-17)] vs -20 [-21 to (-18)] %, p = 0.005), otherwise there were no differences in LV or RV mass or function. WD patients had lower stress perfusion and MPR (2.95 [2.74-3.29] vs 3.81 [2.67-4.45] mL/min/g, and 3.3 [3.1-3.8] vs 5.0 [2.9-5.4]), while ECV was higher (29 [28-30] vs 26 [26-29] %), p<0.05 for all, but there were no other differences in multiparametric mapping results. ECV did not correlate with strain parameters. ECV was associated with WD and sex but not age (WD β = 2.58%, male sex β = -0.03%, model R² 0.41, p<0.05 for all). LGE was present in the RV insertion point in 12/17 (71%) of WD patients.

In this study, stable WD patients without apparent cardiac symptoms have early signs of diffuse fibrosis, coronary microvascular dysfunction, and worse systolic function. However, this study is limited by small sample size limiting further subgroup analysis, lack of both longitudinal clinical data and biopsies, not allowing for correlation of CMR findings to histopathology.